U.S. Food and Drug Administration approval: ruxolitinib for the treatment of patients with intermediate and high-risk myelofibrosis.

Abstract

On November 16, 2011, the U.S. Food and Drug Administration (FDA) granted full approval to ruxolitinib, (Jakafi; Incyte Corp.), an inhibitor of the Janus kinases 1 and 2, for the treatment of patients with intermediate- or high-risk myelofibrosis, including primary myelofibrosis, postpolycythemia vera myelofibrosis, and postessential thrombocythemia myelofibrosis. This approval was based on the results of 2 large randomized phase III trials that enrolled patients with intermediate-2 or high-risk myelofibrosis and compared ruxolitinib with placebo (study 1) or best available therapy (study 2). The primary efficacy endpoint was the proportion of patients who experienced a reduction in spleen volume of ≥ 35% at 24 weeks (study 1) or 48 weeks (study 2). The key secondary endpoint in study 1 was the proportion of patients who experienced a ≥ 50% improvement from baseline in myelofibrosis total symptom score at 24 weeks. The results of these studies showed that a greater proportion of patients treated with ruxolitinib experienced a ≥ 35% reduction in spleen volume as compared with those treated with placebo (42% vs. 1%, P < 0.0001) or best available therapy (29% vs. 0%, P < 0.0001). A greater proportion of patients in study 1 experienced a ≥ 50% reduction in the myelofibrosis total symptom score during treatment with ruxolitinib than with placebo (46% vs. 5%, P < 0.0001). Ruxolitinib treatment was associated with an increased incidence of grades III and IV anemia, thrombocytopenia, and neutropenia. This is the first drug approved for myelofibrosis.

• Authors: Albert Deisseroth, Edvardas Kaminskas, Joseph Grillo, Wei Chen, Haleh Saber, Hong L Lu, Mark D Rothmann, Satjit Brar, Jian Wang, Christine Garnett, Julie Bullock, Laurie B Burke, Atiqur Rahman, Rajeshwari Sridhara, Ann Farrell, Richard Pazdur
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 18 Issue 12 Pg. 3212-7 (Jun 15 2012) ISSN: 1557-3265 [Electronic] United States
• PMID: 22544377 (Publication Type: Journal Article)
• Copyright: ©2012 AACR.

Chemical References

• Nitriles
• Pyrazoles
• Pyrimidines
• ruxolitinib
• Janus Kinase 1
• Janus Kinase 2

Topics

• Anemia (chemically induced)
• Clinical Trials, Phase III as Topic
• Drug Approval
• Female
• Humans
• Janus Kinase 1 (antagonists & inhibitors)
• Janus Kinase 2 (antagonists & inhibitors)
• Male
• Neutropenia (chemically induced)
• Nitriles
• Primary Myelofibrosis (drug therapy)
• Pyrazoles (adverse effects, pharmacology, therapeutic use)
• Pyrimidines
• Randomized Controlled Trials as Topic
• Thrombocytopenia (chemically induced)
• United States
• United States Food and Drug Administration